Expression and Function of Sodium/Hydrogen Exchangers in Preimplantation Mouse Embryos.
Bibliographic record
Abstract
Intracellular pH (pHi) affects many cellular mechanisms including gene expression, cellular metabolism, calcium homeostasis, cell volume regulation, proliferation and survival. Most cells use two general pHi-regulatory mechanisms; the HCO3−/Cl− (AE, Slc4a family) to reduce internal alkaline load, and the Na+/H+ antiporters (NHE, Slc9a, family) that protect cells from acidosis. Previous studies with preimplantation (PI) embryos have shown robust activity of HCO3−/Cl− exchanger in all stages of development. It was also determined that inhibition of this exchange with the stilbene AE inhibitor DIDS was detrimental to embryo development from 2-cell stage to blastocyst when cultured at high external pH. In this study we elucidated the role of Na+/H+ exchangers as pHi regulators and their role in embryo development in the preimplantation stages. Five of the ten known isoforms of NHE exchangers are located in the plasma membrane. Of these, transcripts for isoforms NHE1, NHE3 and NHE4 were previously reported present in either oocytes or preimplantation embryos. However, it is not established what role, if any, each isoform played in pH regulation and PI embryo development. In this study we investigated the role of each isoform in PI embryos with the aid of isoform selective inhibitors: cariporide and S3226, which selectively inhibit NHE1 and NHE3, respectively. We have found that NHE1 is present and active in all PI stages and regulates embryo recovery from experimentally-induced acute intracellular acidosis. Although transcripts for NHE3 and 4 were also found in the early preimplantation stages (but not NHE2 or NHE5), no detectable activity could be attributed to these isoforms. We have also determined whether prolonged exposure to external acidosis in the presence of the NHE1 inhibitor cariporide was detrimental to healthy embryo development. No difference in survival rates to the blastocyst stage in the presence or absence of cariporide at low external pH was observed over a range of pH levels (6.5-7.3). However, differential staining of blastocysts revealed that embryos cultured at low pH in the presence of cariporide exhibited a significant decrease in ICM cells when compared to control groups under the same conditions, indicating a requirement for NHE1 in optimal preimplantation embryo development.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".